Ch. 9 - Carboxylic Acid Derivatives

11% of MCAT Organic content

What are amides and how are they named?

Formation: Condensation products of carboxylic acids and ammonia or amines.

• Suffix: –amide.

• Substituents on nitrogen: Named with the prefix N–.

• Cyclic amides: Called lactams, named by the Greek letter of the carbon forming the bond with nitrogen (e.g., β-lactam, γ-lactam).

What are esters and how are they named?

Formation: Condensation products of carboxylic acids with alcohols (Fischer esterification).

• Suffix: –oate.

• Esterifying group: Written as a substituent without a number.

• Cyclic esters: Called lactones, named by the number of carbons in the ring and the Greek letter of the carbon forming the bond with oxygen (e.g., α-acetolactone, β-propiolactone).

What are triacylglycerols?

Fat storage molecules with three ester bonds between glycerol and fatty acids.

What is saponification?

Breakdown of fat using a strong base to form soap (salts of long-chain carboxylic acids).

What are anhydrides and how are they named?

Formation: Condensation dimers of carboxylic acids.

• Symmetric anhydrides: Named for the parent carboxylic acid + anhydride.

• Asymmetric anhydrides: Name parent carboxylic acids alphabetically + anhydride.

• Cyclic anhydrides: Formed by heating dioic acids; five- or six-membered rings are generally stable.

What is the reactivity order of carboxylic acid derivatives in nucleophilic substitution?

Anhydrides > Esters > Amides.

What factors influence reactivity in nucleophilic substitution?

Decrease reactivity:

• Steric hindrance: Crowding around the reactive site slows or prevents reactions.

• Protecting groups: Acetals can be used to increase steric hindrance.

Increase reactivity:

• Ring strain: Increased strain (e.g., in β-lactams) makes molecules more reactive.

• Induction: Uneven charge distribution across a σ bond increases reactivity with more electronegative groups.

• Conjugation: Alternating single and multiple bonds increase reactivity by stabilizing transition states.

Why are β-lactams prone to hydrolysis?

Significant ring strain due to:

• Torsional strain: From eclipsing interactions.

• Angle strain: From compressed bond angles below 109.5°.

What are nucleophilic acyl substitution reactions, and how do they differ between derivatives?

• All carboxylic acid derivatives can undergo nucleophilic substitution.

• Rates depend on relative reactivity.

What happens when anhydrides are cleaved by nucleophiles?

• Ammonia/amine: Produces an amide and a carboxylic acid.

• Alcohol: Produces an ester and a carboxylic acid.

• Water: Produces two carboxylic acids.

What is transesterification?

• Exchange of one esterifying group for another on an ester.

• Nucleophile: An alcohol.

How are amides hydrolyzed?

• Conditions: Strongly acidic or basic.

• Nucleophile: Water or hydroxide anion.

• Product: Carboxylic acid.